MEKK3-TGFß crosstalk regulates inward arterial remodeling.

Arterial remodeling is an important adaptive mechanism that maintains normal fluid shear stress in a variety of physiologic and pathologic conditions. Inward remodeling, a process that leads to reduction in arterial diameter, plays a critical role in progression of such common diseases as hypertension and atherosclerosis. Yet, despite its pathogenic importance, molecular mechanisms controlling inward remodeling remain undefined. Mitogen-activated protein kinases (MAPKs) perform a number of functions ranging from control of proliferation to migration and cell-fate transitions. While the MAPK ERK1/2 signaling pathway has been extensively examined in the endothelium, less is known about the role of the MEKK3/ERK5 pathway in vascular remodeling. To better define the role played by this signaling cascade, we studied the effect of endothelial-specific deletion of its key upstream MAP3K, MEKK3, in adult mice. The gene's deletion resulted in a gradual inward remodeling of both pulmonary and systematic arteries, leading to spontaneous hypertension in both vascular circuits and accelerated progression of atherosclerosis in hyperlipidemic mice. Molecular analysis revealed activation of TGFß-signaling both in vitro and in vivo. Endothelial-specific TGFßR1 knockout prevented inward arterial remodeling in MEKK3 endothelial knockout mice. These data point to the unexpected participation of endothelial MEKK3 in regulation of TGFßR1-Smad2/3 signaling and inward arterial remodeling in artery diseases.

Assessment of Vascular Indices by Abdominal Aortic Ultrasonography in Preterm Neonates with Bronchopulmonary Dysplasia.

Preterm infants with bronchopulmonary dysplasia (BPD) frequently encounter systemic hypertension, yet the underlying cause remains elusive. Given the absence of prior investigations concerning the correlation between systemic hypertension and aortic thickness, we undertook this study to assess and juxtapose diverse vascular indices amidst preterm neonates with BPD, preterm neonates lacking BPD, and healthy neonates, utilizing abdominal aorta ultrasonography. This cross-sectional study encompassed 20 preterm neonates, 20 preterm neonates with BPD, and 20 healthy neonates, meticulously matched for sex and postnatal age. Comprehensive demographic, anthropometric, and clinical evaluation data were documented. The neonates underwent abdominal aortic ultrasonography for comparative evaluation of aortic wall thickness and vasomotor function across the three groups. The study revealed that neonates with BPD exhibited a notably higher average systolic blood pressure than preterm and term neonates (P < 0.05). Conversely, echocardiographic parameters such as input impedance, and arterial wall stiffness index displayed no substantial variance among the three groups (P > 0.05). The mean (SD) aortic intima-media thickness (aIMT) for preterm neonates with BPD, preterm neonates, and term neonates were 814 (193.59) µm, 497.50 (172.19) µm, and 574.00 (113.20) µm, correspondingly (P < 0.05). Furthermore, the mean (SD) pulsatile diameter for preterm neonates with BPD, preterm neonates, and term neonates were 1.52 (0.81) mm, 0.91 (0.55) mm, and 1.34 (0.51) mm, respectively (P < 0.05). Following adjustment for birth weight, sex, and gestational age at birth, the study identified a noteworthy correlation between aIMT and BPD. The investigation concluded that the mean aortic intima-media thickness (aIMT) was significantly elevated in preterm neonates with BPD, signifying a potential early indicator of atherosclerosis and predisposition to future heightened blood pressure and cardiovascular ailments. Consequently, the study postulates that aIMT could be a consistent and well-tolerated marker for identifying BPD patients at risk of developing these health complications.

Blood Pressure and Glaucomatous Progression in a Large Clinical Population.

PURPOSE: To investigate the effect of systemic arterial blood pressure (BP) on rates of progressive structural damage over time in glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 7501 eyes of 3976 subjects with glaucoma or suspected of glaucoma followed over time from the Duke Glaucoma Registry. METHODS: Linear mixed models were used to investigate the effects of BP on the rates of retinal nerve fiber layer (RNFL) loss from spectral-domain OCT (SD-OCT) over time. Models were adjusted for intraocular pressure (IOP), gender, race, diagnosis, central corneal thickness (CCT), follow-up time, and baseline disease severity. MAIN OUTCOME MEASURE: Effect of mean arterial pressure (MAP), systolic arterial pressure (SAP), and diastolic arterial pressure (DAP) on rates of RNFL loss over time. RESULTS: A total of 157 291 BP visits, 45 408 IOP visits, and 30 238 SD-OCT visits were included. Mean rate of RNFL change was -0.70 µm/year (95% confidence interval, -0.72 to -0.67 µm/year). In univariable models, MAP, SAP, and DAP during follow-up were not significantly associated with rates of RNFL loss. However, when adjusted for mean IOP during follow-up, each 10 mmHg reduction in mean MAP (-0.06 µm/year; P = 0.007) and mean DAP (-0.08 µm/year; P < 0.001) but not SAP (-0.01 µm/year; P = 0.355) was associated with significantly faster rates of RNFL thickness change over time. The effect of the arterial pressure metrics remained significant after additional adjustment for baseline age, diagnosis, sex, race, follow-up time, disease severity, and corneal thickness. CONCLUSIONS: When adjusted for IOP, lower MAP and DAP during follow-up were significantly associated with faster rates of RNFL loss, suggesting that levels of systemic BP may be a significant factor in glaucoma progression.

Cardiovascular Prevention Among Young Adults with Congenital Heart Disease.

PURPOSE OF REVIEW: There are over a million adults living with congenital heart disease (CHD) in the USA. There have been improvements in CHD management which have led to an expansion of the adult congenital heart disease (ACHD) population. There is a high prevalence of atherosclerotic cardiovascular disease (ASCVD) encountered in the aging ACHD population. This review focuses on the most recent literature regarding the primary prevention of ASCVD in young ACHD patients. RECENT FINDINGS: There are unique considerations for ASCVD risk reduction in ACHD patients. ASCVD may be as prevalent in ACHD compared in the general population. However, there may be a perceived shorter life expectancy in ACHD patients; therefore, primary prevention of ASCVD may not be considered important. Preventative strategies for ASCVD are underutilized in ACHD patients. As these patients are followed for a lifetime by cardiologists, we can truly pursue primary prevention in this aging population.

The effect of calcium channel blocker (CCB) treatment on retinal and choroidal vessels in a group of hypertensive patients.

PURPOSE: The present study was designed to observe the vasoreactivity in retina and choroid after calcium channel blocker (CCB) treatment in a group of hypertensive patients. METHOD: The study was based on 56 hypertensive patients (56 eyes) and 56 control subjects (56 eyes). Choroidal scans and the measurement of peripapillary retinal vessel diameters was performed at baseline and optical coherence tomography (OCT) scans were also performed at first month . Subfoveal choroidal thickness (SFCT) and the diameters of superior temporal artery (STA), inferior temporal artery (ITA), superior temporal vein (STV), inferior temporal vein (ITV) were compared between the groups. RESULTS: The baseline diameters of the STA, ITA were significantly decreased in the patient group compared with the control group (all p < .05). There was a significant increase at first month after the CCB treatment in comparison to baseline measurements (all p < .05). When compared with the controls, the diameter of venules showed a decrease at baseline but was not significant. After the treatment, the diameters of venules were insignificantly increased compared with baseline measurements (p = .178 and p = .275) and there were also no significant differences between the control group and the patient group in first month (all p > .05). The average choroidal thickness measurements of the hypertensive group was lower than the control group (p = .404) and there was a tendency to increase after the treatment (p = .055). CONCLUSION: This study demonstrates that, treatment with CCB seems to improve retinal arteries and has almost no affect on the choroidal thickness in newly diagnosed hypertensive patients.

An observational thoracic radiographic study of aortic remodeling in dogs with confirmed systemic hypertension.

Sustained systemic hypertension (SH) has been shown to cause target organ damage to various tissues in dogs and cats, including the aorta. Aortic dilatation occurs most commonly secondary to SH in people and develops prior to an aortic aneurysm. Our hypothesis was that blinded reviewers could be trained to recognize variable alterations of aortic shape and size on thoracic radiographs of canine patients with SH. A retrospective, observational, cross-sectional study was performed with three blinded reviewers evaluating thoracic radiographic images of 21 dogs with normal blood pressure compared to 145 dogs with system hypertension. Lateral radiographs showed variable aortic undulation and disproportionate enlargement of a portion of the aorta between the ascending and proximal descending aorta compared to the descending aorta just cranial to the diaphragm. On orthogonal projections, the aortic arch to proximal descending aorta bowed laterally similar to changes reported in people with the formation of an aortic "knob." After completing a training module, reviewers of the thoracic images had a 74% agreement with Fleiss' Kappa of 0.50 indicating moderate agreement recognizing SH changes to the thoracic aorta. The more experienced blinded reviewers had accuracies of 85% and 80% for identifying systemic hypertension, slightly better than the less experienced reviewer at 76%. The ratio of thoracic cavity width to aortic knob width was significantly different between the groups (median ratio 3.4 SH vs 4.1 normal). Evidence of target organ damage (TOD) to the thoracic aorta may prompt earlier recognition and treatment for systemic hypertension.

Short-term effect of angiotensin-converting enzyme inhibitor on retinal vessel diameter in patients with systemic hypertension.

PURPOSE: To determine the retinal vessel diameter changes after angiotensin-converting enzyme (ACE) inhibitor treatment in a group of hypertensive patients. METHODS: This study included 60 treatment-naive hypertensive patients who were treated with ACE inhibitor. Sixty healthy volunteers served as control group. An optical coherence tomography scan protocol including the measurement of peripapillary retinal vessel diameters was performed at baseline and at 1st month. The diameters of superior temporal artery (STA), inferior temporal artery (ITA), superior temporal vein (STV), inferior temporal vein (ITV), superior nasal artery (SNA), inferior nasal artery (INA), superior nasal vein (SNV) and inferior nasal vein (INV) were statistically compared. RESULTS: The baseline diameters of the STA, ITA, SNA, and INA were significantly decreased in the patient group compared with the control group (all p < 0.05). There was a significant increase at 1st month after the treatment in comparison to baseline measurements (all p < 0.05). When compared with the controls, only the diameter of SNV showed a significant decrease at baseline (p = 0.031). After the treatment, the diameters of SNV and INV were significantly increased compared with baseline measurements (p = 0.049 and p = 0.035, respectively). There were no significant differences between the control group and the patient group at 1st month (all p > 0.05). CONCLUSION: Short-term treatment with ACE inhibitor led to a significant improvement in the retinal vessel diameters of patients with hypertension.

AHR canonical pathway: in vivo findings to support novel antihypertensive strategies.

Essential hypertension (HTN) is a disease where genetic and environmental factors interact to produce a high prevalent set of almost indistinguishable phenotypes. The weak definition of what is under the umbrella of HTN is a consequence of the lack of knowledge on the players involved in environment-gene interaction and their impact on blood pressure (BP) and mechanisms. The disclosure of these mechanisms that sense and (mal)adapt to toxic-environmental stimuli might at least determine some phenotypes of essential HTN and will have important therapeutic implications. In the present manuscript, we looked closer to the environmental sensor aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor involved in cardiovascular physiology, but better known by its involvement in biotransformation of xenobiotics through its canonical pathway. This review aims to disclose the contribution of the AHR-canonical pathway to HTN. For better mirror the complexity of the mechanisms involved in BP regulation, we privileged evidence from in vivo studies. Here we ascertained the level of available evidence and a comprehensive characterization of the AHR-related phenotype of HTN. We reviewed clinical and rodent studies on AHR-HTN genetic association and on AHR ligands and their impact on BP. We concluded that AHR is a druggable mechanistic linker of environmental exposure to HTN. We conclude that is worth to investigate the canonical pathway of AHR and the expression/polymorphisms of its related genes and/or other biomarkers (e.g. tryptophan-related ligands), in order to identify patients that may benefit from an AHR-centered antihypertensive treatment.

Burden and correlates of cognitive impairment among hypertensive patients in Tanzania: a cross-sectional study.

BACKGROUND: The evolution of cognitive impairment of vascular origin is increasingly becoming a prominent health threat particularly in this era where hypertension is the leading contributor of global disease burden and overall health loss. Hypertension is associated with the alteration of the cerebral microcirculation coupled by unfavorable vascular remodeling with consequential slowing of mental processing speed, reduced abstract reasoning, loss of linguistic abilities, and attention and memory deficits. Owing to the rapidly rising burden of hypertension in Tanzania, we sought to assess the prevalence and correlates of cognitive impairment among hypertensive patients attending a tertiary cardiovascular hospital in Tanzania. METHODOLOGY: A hospital-based cross-sectional study was conducted at Jakaya Kikwete Cardiac Institute, a tertiary care public teaching hospital in Dar es Salaam, Tanzania between March 2020 and February 2021. A consecutive sampling method was utilized to recruit consented hypertensive outpatients during their scheduled clinic visit. General Practitioner Assessment of Cognition (GPCOG) Score was utilized in the assessment of cognitive functions. All statistical analyses utilized STATA v11.0 software. Pearson Chi square and Student's T-test were used to compare categorical and continuous variables respectively. Logistic regression analyses were used to assess for factors associated with cognitive impairment. Odd ratios with 95% confidence intervals and p-values are reported. All tests were 2-sided and p < 0.05 was used to denote a statistical significance. RESULTS: A total of 1201 hypertensive patients were enrolled in this study. The mean age was 58.1 years and females constituted nearly two-thirds of the study population. About three quarters had excess body weight, 16.6% had diabetes, 7.7% had history of stroke, 5.7% had heart failure, 16.7% had renal dysfunction, 53.7% had anemia, 27.7% had hypertriglyceridemia, 38.5% had elevated LDL, and 2.4% were HIV-infected. Nearly two-thirds of participants had uncontrolled blood pressure and 8.7% had orthostatic hypotension. Overall, 524 (43.6%) of participants had cognitive impairment. During bivariate analysis in a logistic regression model of 16 characteristics, 14 parameters showed association with cognitive functions. However, after controlling for confounders, multivariate analysis revealed ≤primary education (OR 3.5, 95%CI 2.4-5.2, p < 0.001), unemployed state (OR 1.7, 95%CI 1.2-2.6, p < 0.01), rural habitation (OR 1.8, 95%CI 1.1-2.9, p = 0.01) and renal dysfunction (OR 1.7, 95%CI 1.0-2.7, p = 0.04) to have independent association with cognitive impairment. CONCLUSION: This present study underscore that cognitive decline is considerably prevalent among individuals with systemic hypertension. In view of this, it is pivotal to incorporate cognitive assessment in routine evaluation of hypertensive patients.

Endothelial to mesenchymal transition during neonatal hyperoxia-induced pulmonary hypertension.

Bronchopulmonary dysplasia (BPD), a chronic lung disease in premature infants, results from mechanical ventilation and hyperoxia, amongst other factors. Although most BPD survivors can be weaned from supplemental oxygen, many show evidence of cardiovascular sequelae in adulthood, including pulmonary hypertension and pulmonary vascular remodeling. Endothelial-mesenchymal transition (EndoMT) plays an important role in mediating vascular remodeling in idiopathic pulmonary arterial hypertension. Whether hyperoxic exposure, a known mediator of BPD in rodent models, causes EndoMT resulting in vascular remodeling and pulmonary hypertension remains unclear. We hypothesized that neonatal hyperoxic exposure causes EndoMT, leading to the development of pulmonary hypertension in adulthood. To test this hypothesis, newborn mice were exposed to hyperoxia and then allowed to recover in room air until adulthood. Neonatal hyperoxic exposure gradually caused pulmonary vascular and right ventricle remodeling as well as pulmonary hypertension. Male mice were more susceptible to developing pulmonary hypertension compared to female mice, when exposed to hyperoxia as newborns. Hyperoxic exposure induced EndoMT in mouse lungs as well as in cultured lung microvascular endothelial cells (LMVECs) isolated from neonatal mice and human fetal donors. This was augmented in cultured LMVECs from male donors compared to those from female donors. Using primary mouse LMVECs, hyperoxic exposure increased phosphorylation of both Smad2 and Smad3, but reduced Smad7 protein levels. Treatment with a selective TGF-ß inhibitor SB431542 blocked hyperoxia-induced EndoMT in vitro. Altogether, we show that neonatal hyperoxic exposure caused vascular remodeling and pulmonary hypertension in adulthood. This was associated with increased EndoMT. These novel observations provide mechanisms underlying hyperoxia-induced vascular remodeling and potential approaches to prevent BPD-associated pulmonary hypertension by targeting EndoMT. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Ocular fundus abnormalities in cats affected by systemic hypertension: Prevalence, characterization, and outcome of treatment.

OBJECTIVES: To determine the prevalence of ocular fundus abnormalities in cats with a diagnosis of systemic hypertension, to characterize the abnormalities observed, and to evaluate ophthalmoscopic evolution during treatment with amlodipine besylate. ANIMALS STUDIED: Cats diagnosed as affected by SHP in a 2-year period. PROCEDURES: Systemic hypertension was assessed by oscillometric blood pressure measurement, and its etiology was also established. All the cats received an ophthalmic examination, and ocular lesions were classified with a score from 0 (no abnormalities) to 4 (severe abnormalities). All cats received amlodipine besylate by mouth, and those that showed fundus abnormalities were regularly rechecked from 7 to 365 days after diagnosis. Data were statistically analyzed to compare Psys and Pdia with all the variables and to correlate Psys and Pdia with the fundus score. RESULTS: A total of 225 cats were enrolled in the study, and the prevalence of fundus abnormalities was 58.6% (21.2%: grade 1; 18.2%: grade 2; 36.4%: grade 3; and 24.2%: grade 4). Systemic hypertension was diagnosed concurrently with chronic renal failure (60.4%), hyperthyroidism (28.9%), both chronic renal failure and hyperthyroidism (7.6%), and hypertrophic myocardiopathy (3.1%). A significant effect of Psys values on the fundus score was detected. Amlodipine therapy improved fundus abnormalities in 50% of cases at the 21-day follow-up. CONCLUSIONS: This study showed that fundus abnormalities are common in hypertensive cats at the time of the systemic diagnosis, and most of the abnormalities are moderate to severe. Treatment with amlodipine appeared to improve ophthalmic lesions over time.

Echocardiographic changes in the shape and size of the aortic cusps in dogs with confirmed systemic hypertension.

Systemic hypertension (SH) in dogs typically occurs secondary to renal disease, diabetes mellitus, hyperadrenocorticism, malignant adrenal tumors, or various medications. Echocardiography performed on people with SH has shown asymmetric dilation of the sinuses at the level of the aortic valves, previously undescribed in canine patients. The objective of this retrospective case-control study was to determine if there was a difference in size and shape of the aortic cusps at the level of the sinus of Valsalva in dogs with SH compared to dogs with normal blood pressure. We reviewed echocardiographic findings in 74 dogs with SH and 37 dogs with normal blood pressure (NBP), defined as less than 150 mmHg. Systemic hypertension was classified as mild (150-159 mm Hg), moderate (160-179 mm Hg), or severe (greater than 180 mm Hg). There was a significant difference (P < .001) in the mean size of the aorta cusps at the level of the sinuses in 67 of 74 dogs with SH and none of 37 dogs with NBP. Of the 74 dogs with SH, 70 had left ventricular hypertrophy (18 asymmetric, 15 concentric, and 37 eccentric). Additionally, there was aortic root dilatation in 15 dogs, aortic insufficiency in 21, mitral regurgitation in 50, and left atrial enlargement in 71. The standard deviation of the three cusp measurements between the dogs with SH and dogs with NBP had a sensitivity of 92% and specificity of 97% for diagnosis of SH. Asymmetric size of the aortic cusps on echocardiography is therefore a reliable indicator of SH in dogs.

Bariatric Surgery: Late Outcomes in Patients Who Reduced Comorbidities at Early Follow-Up.

Backgroundand Objectives: In severe obesity, a relevant weight loss can promote the reduction of comorbidities, such as systemic arterial hypertension (SAH), dyslipidemia, and diabetes mellitus (DM2). Bariatric surgery (BS) has been an essential resource in the therapy of this disease with a short-term reduction of cardiometabolic risk (CR). This study aimed to evaluate the reduction of factors associated with the CR in patients undergoing BS at a 5-year follow-up. Materials and Methods: This is a longitudinal, retrospective study carried out with patients undergoing BS by the Brazilian Public Healthcare System (PHS). Anthropometric and clinical parameters related to the CR (DM2, dyslipidemia, and SAH), quantified by the Assessment of Obesity-Related Comorbidities (AORC) score, were evaluated at the following moments: admission and preoperative and postoperative returns (3 months, 6 months, 1 to 5 years). Results: The sample had a mean age of 44.69 ± 9.49 years and were predominantly in the age group 20-29 years (34.80%) and women (72.46%). At admission to the service, 42.3% had DM2, 50.7% dyslipidemia, and 78.9% SAH. Regarding BS, the gastric bypass technique was used in 92.86% of the sample, and the waiting time for the procedure was 28.3 ± 24.4 months. In the pre- and postoperative period of 3 months, there was a significant reduction in the frequency of DM2 (p < 0.003), dyslipidemia (p < 0.000), and SAH (p < 0.000). However, at postoperative follow-up from 6 months to 5 years, there was no significant reduction in the comorbidities studied. After five years, 35.7% had total remission of DM2 and 2.9% partial remission of DM2, 44.2% had control and remission of dyslipidemia, and 19.6% of SAH (AORC score ≤ 2 for the comorbidities). Conclusion: BS promoted a reduction of the CR in the first three months after BS in severely obese PHS users.

Sex-Related Differences in the Impact of Systemic Hypertension on Left Ventricular Remodeling in Patients with Hypertrophic Obstructive Cardiomyopathy.

BACKGROUND: The clinical condition of hypertrophic obstructive cardiomyopathy (HOCM) and concomitant systemic hypertension is growing more and more prevalent, and it brings about a challenging diagnostic and therapeutic dilemma. However, whether systemic hypertension has an impact on HOCM, and whether sex-related differences exist in this impact, remains unclear. METHODS: A total of 453 HOCM patients (age 48.7 ± 12.8 years, 252 [55.6%] males) were recruited in this study. There were 150 patients (33.1%, 81 males and 69 females) with a history of controlled systemic hypertension. Cardiac magnetic resonance (CMR) imaging was performed in all patients. Left ventricular (LV) remodeling index (LVRI) was determined by CMR. LVRI >1.3 g/mL was defined as pathological LV remodeling. RESULTS: Men had significantly greater LVRI (1.40 ± 0.54 vs. 1.15 ± 0.38 g/mL, p < 0.001) and LVRI >1.3 g/mL (p = 0.002), compared with women. The incidence of syncope and 5-year sudden cardiac death risk score were significantly lower in HOCM with hypertension than those without hypertension. LVRI (p = 0.003) and LVRI >1.3 g/mL (p = 0.007) were significantly smaller in males with hypertension, but not in females with hypertension. However, log cardiac troponin I and log N-terminal pro-B-type natriuretic peptide were positively correlated with LVRI in men and women. On multivariable logistic analysis, hypertension (OR 0.172, 95% CI 0.056-0.528, p = 0.002) remained an independent determinant of pathological LV remodeling in males, whereas not in females. CONCLUSIONS: There were significant sex differences in the impact of systemic hypertension on LV remodeling in patients with HOCM. Controlled systemic hypertension may contribute to improving LV remodeling in male patients with HOCM, but not in females.

Four-Dimensional Volume-Strain Expression in Asymptomatic Primary Hypertension Patients Presenting with Subclinical Left Atrium-Ventricle Dysfunction.

OBJECTIVE: The purpose of this study was to evaluate the different components of left atrial (LA) dysfunction predictors in asymptomatic primary systemic hypertension patients with preserved left ventricular (LV) ejection fraction, particularly using LA 4-dimensional (4D) longitudinal and circumferential strain values. METHODS AND RESULTS: Patients with no left ventricular hypertrophy (NLVH) and left ventricular hypertrophy (LVH) are all asymptomatic regarding primary blood hypertension. Thirty NLVH patients and 30 LVH patients according to LV mass index and 40 controls analyzed by 4D echocardiography were prospectively enrolled. LA volumes and longitudinal and circumferential strains were measured using 4D volume-strain echocardiography with a Vivid E95 Version 203 instrument. Correlation analysis indicated a significant relation between LV 4D mass index and LA 4D longitudinal/circumferential strain (r = -0.446 to 0.381, p = 0.000-0.042). LVH patients had a reduced LA emptying fraction compared with NLVH patients and control subjects (p < 0.01). NLVH patients had an impaired LA conduit function and increased contractile function compared with the control group (p < 0.01). LVH patients had increased LA volumes and significantly decreased reservoir, conduit and contractile functions compared with the controls (p < 0.01). LVH patients had increased LA volumes and decreased reservoir and contractile functions compared with NLVH patients (p < 0.01). The clinical utility of LA 4D volume-strain measurement was verified by receiver-operating characteristic curve analysis showing larger net benefits as evaluated with NLVH, LVH and control group comparisons. Interclass correlation coefficients of interobserver and intraobserver assessments in the LV and LA 4D value evaluations were >0.75 and >0.85, respectively. CONCLUSIONS: LVH patients showed increased LA volumes and decreased LA emptying fractions. LA reservoir, conduit and contractile functions were significantly impaired in LVH patients. Decreased LA conduit function and increased contractile function were revealed in NLVH patients. LA volumetric and functional analyses with 4D volume-strain echocardiography may facilitate the recognition of subtle LA and LV dysfunctions in asymptomatic systemic hypertension patients.

Long-Term Follow-Up Changes of Central Choroidal Thickness Thinning after Repeated Anti-VEGF Therapy Injections in Patients with Central Retinal Vein Occlusion-Related Macular Edema with Systemic Hypertension.

PURPOSE: We investigated the thinning of central choroidal thickness (CCT) following intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs to treat central retinal vein occlusion (CRVO)-related macular edema in patients with and without systemic hypertension (HT) to assess the influence of repeated anti-VEGF therapy and HT on the choroid in CRVO eyes. METHODS: We conducted a retrospective study involving 27 patients with CRVO-related macular edema from January 2014 to July 2017, with follow-ups exceeding 18 months. Visual acuity (VA), central retinal thickness (CRT), and CCT were evaluated before and after initial anti-VEGF drug treatment during follow-up. RESULTS: The mean follow-up period was 35.2 months. Seventeen (63.0%) patients had HT. At 1 month after treatment, VA had improved in 21 (77.8%) patients, and CRT had decreased in 25 (92.6%). At the final visit, 22 (81.5%) showed improved VA, 19 (70.4%) had resolved macular edema, and the CCT had gradually become thinner with additional drug injections in all the patients. Furthermore, the mean CCT in HT patients (209.0 µm) was significantly lower than in non-HT patients (256.1 µm), and the mean injections were 7.8 and 5.3, respectively (p = 0.2067). CONCLUSION: The CCTs were thinner in eyes with HT than in eyes without HT both before and after the repeated anti-VEGF injections.

Can ocular OCT findings be as a predictor for end-organ damage in systemic hypertension?

PURPOSE: Detection of end-organ damage (EOD) in systemic hypertension is essential for the management of systemic hypertension. We aimed to evaluate subfoveal choroidal thickness (SFCT) and retinal layers' thicknesses by using spectral domain optical coherence tomography (SD­OCT) in patients with systemic hypertension and to assess the relationship between EOD and SD-OCT parameters. METHODS: A total of 189 consecutive patients with systemic hypertension and 100 controls were included. Patients were examined to detect EOD including hypertensive retinopathy (HTRP), left ventricular hypertrophy assessed by transthoracic echocardiography and microalbuminuria assessed by 24-h urine analysis. SFCT, inner plexiform-ganglion cell complex (IP-GCC), peripapillary retinal nerve fiber layer (pRNFL) and central macular thickness (CMT) were measured with SD-OCT. RESULTS: Patients with systemic hypertension had significantly lower SFCT and retinal layer thicknesses than controls (P˂0.001). In the dilated fundus photographic evaluation, 94 patients with systemic hypertension had HTRP and these patients had lower SFCT, CMT, IP-GCC and pRNFL thicknesses compared to hypertensive patients without HTRP and healthy controls. Patients with EOD had significantly lower SFCT, CMT, IP-GCC and pRNFL thicknesses and as the number of EOD increased, the SFCT decreased significantly. In the multivariate analysis, SFCT was found as an independent predictor of EOD (P˂0.001, odds ratio: 0.0605). CONCLUSION: Hypertensive patients, especially with EOD had significantly lower SD-OCT parameters compared to controls. It would be rational to add SD-OCT assessment to conventional hypertensive retinopathy evaluation in patients with systemic hypertension for early diagnosis of end-organ damage, burden of target organ involvement and monitoring anti-hypertensive treatment.

Iris aneurysm in feline hypertensive oculopathy.

OBJECTIVE: To describe and document the prevalence and cause of iris aneurysm in feline hypertensive oculopathy. ANIMALS STUDIED: Privately owned cats with systemic hypertension presented for sudden visual deficits and/or hyphema. PROCEDURES: A retrospective search of medical records of cats with systemic hypertension was performed in a specialized eye practice from October 2001 to August 2016. Inclusion criteria used for further evaluation were (1) systolic blood pressure exceeding 170 mm Hg measured by Doppler ultrasound, (2) typical fundus changes consistent with systemic hypertension (retinal folds, retinal edema, intraretinal bullous fluid accumulation, retinal detachment-partial or total, intra-/preretinal bleeding) in at least one eye, and (3) at least one follow-up visit with documented response to therapy with amlodipine. Cats with bilateral hyphema were excluded. RESULTS: A total of 206 cats fulfilled the inclusion criteria. Twenty-eight cats (14%) showed an aneurysm of the iridal vessels, 21 75% with some amount of hyphema. In total, hyphema was present in 62 cats (30%). Pearson correlation of fundus changes, hyphema, and aneurysm was performed. A high correlation between fundus changes without posterior segment hemorrhage and hyphema was found. The histopathology of one eye showed iridial vascular changes compatible with an aneurysm. In 75 cats, additional blood analysis was performed. Presumed chronic kidney disease (80%) was the most common cause of systemic hypertension with eye disease, followed by hyperthyroidism (20%). CONCLUSION: Vascular changes of the iris compatible with aneurysms were seen in 14% of cats with systemic hypertension and may result in vascular rupture and acute hyphema.

Early Programming of Adult Systemic Essential Hypertension.

Cardiovascular diseases are being included in the study of developmental origins of health and disease (DOHaD) and essential systemic hypertension has also been added to this field. Epigenetic modifications are one of the main mechanisms leading to early programming of disease. Different environmental factors occurring during critical windows in the early stages of life may leave epigenetic cues, which may be involved in the programming of hypertension when individuals reach adulthood. Such environmental factors include pre-term birth, low weight at birth, altered programming of different organs such as the blood vessels and the kidney, and living in disadvantageous conditions in the programming of hypertension. Mechanisms behind these factors that impact on the programming include undernutrition, oxidative stress, inflammation, emotional stress, and changes in the microbiota. These factors and their underlying causes acting at the vascular level will be discussed in this paper. We also explore the establishment of epigenetic cues that may lead to hypertension at the vascular level such as DNA methylation, histone modifications (methylation and acetylation), and the role of microRNAs in the endothelial cells and blood vessel smooth muscle which participate in hypertension. Since epigenetic changes are reversible, the knowledge of this type of markers could be useful in the field of prevention, diagnosis or epigenetic drugs as a therapeutic approach to hypertension.

Aortic to caudal vena cava ratio measurements using abdominal ultrasound are increased in dogs with confirmed systemic hypertension.

Chronically sustained systemic hypertension in dogs can damage the kidneys, eye, brain, heart, and vessels. In human medicine, systemic hypertension has been implicated as the most common risk factor for aorta dilation, which can progress to an aneurysm. Abdominal ultrasound has been commonly used to monitor the size of the abdominal aorta in people with systemic hypertension. In this retrospective cross-sectional abdominal ultrasound study, evaluation of the size of the abdominal aorta relative to the caudal vena cava was performed in 18 control dogs and 128 dogs with confirmed systemic hypertension. Preexisting conditions contributing to systemic hypertension in these dogs were renal disease, hyperadrenocorticism, diabetes mellitus, adrenal tumors, and previous administration of phenylpropanolamine or palladia. The abdominal aorta and caudal vena cava were assessed from longitudinal images cranial to the trifurcation with measurements made from outer border to outer border of the walls, being careful not to compress the caudal vena cava that would alter its size. Our hypothesis was the ratio of the diameter of the abdominal aorta to caudal vena cava would be higher in dogs with systemic hypertension compared to dogs with normal blood pressure. The mean abdominal aorta-caudal vena cava ratio was 1.028 in control dogs with a normal blood pressure and 1.515 in dogs with systemic hypertension. In dogs with confirmed systemic hypertension, the abdominal aorta was dilated compared to the caudal vena cava in the caudal abdomen. An increase in the abdominal aorta-caudal vena cava ratio in a dog should raise suspicion for the presence of systemic hypertension and prompt evaluation of blood pressure.